Oncology Therapeutics Targeting the Metabolism of Amino Acids

Cells. 2020 Aug 15;9(8):1904. doi: 10.3390/cells9081904.

Abstract

Amino acid metabolism promotes cancer cell proliferation and survival by supporting building block synthesis, producing reducing agents to mitigate oxidative stress, and generating immunosuppressive metabolites for immune evasion. Malignant cells rewire amino acid metabolism to maximize their access to nutrients. Amino acid transporter expression is upregulated to acquire amino acids from the extracellular environment. Under nutrient depleted conditions, macropinocytosis can be activated where proteins from the extracellular environment are engulfed and degraded into the constituent amino acids. The demand for non-essential amino acids (NEAAs) can be met through de novo synthesis pathways. Cancer cells can alter various signaling pathways to boost amino acid usage for the generation of nucleotides, reactive oxygen species (ROS) scavenging molecules, and oncometabolites. The importance of amino acid metabolism in cancer proliferation makes it a potential target for therapeutic intervention, including via small molecules and antibodies. In this review, we will delineate the targets related to amino acid metabolism and promising therapeutic approaches.

Keywords: amino acids; cancer metabolism; oncogenic therapeutics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Transport Systems / antagonists & inhibitors
  • Amino Acid Transport Systems / metabolism
  • Amino Acids / antagonists & inhibitors*
  • Amino Acids / metabolism*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use*
  • Cell Proliferation / drug effects
  • Humans
  • Molecular Targeted Therapy / methods*
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Oxidative Stress / drug effects
  • Pinocytosis / drug effects
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*

Substances

  • Amino Acid Transport Systems
  • Amino Acids
  • Antineoplastic Agents
  • Reactive Oxygen Species